CA2468957A1 - Methods of propagation of influenza virus in cell lines over expressing sialyl transferases - Google Patents

Methods of propagation of influenza virus in cell lines over expressing sialyl transferases Download PDF

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Publication number
CA2468957A1
CA2468957A1 CA002468957A CA2468957A CA2468957A1 CA 2468957 A1 CA2468957 A1 CA 2468957A1 CA 002468957 A CA002468957 A CA 002468957A CA 2468957 A CA2468957 A CA 2468957A CA 2468957 A1 CA2468957 A1 CA 2468957A1
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cell
influenza
virus particle
sialyltransferase
human
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CA002468957A
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French (fr)
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CA2468957C (en
Inventor
Giuseppe Marzio
Maria Grazia Pau
Dirk Jan Elbertus Opstelten
Alphonsus Gerardus Cornelis Maria Uytdehaag
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Janssen Vaccines and Prevention BV
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    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/005—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from viruses
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K39/12—Viral antigens
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K39/12—Viral antigens
    • A61K39/145—Orthomyxoviridae, e.g. influenza virus
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A61P31/14—Antivirals for RNA viruses
    • A61P31/16—Antivirals for RNA viruses for influenza or rhinoviruses
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
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    • C12N7/00—Viruses; Bacteriophages; Compositions thereof; Preparation or purification thereof
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    • C12N7/00—Viruses; Bacteriophages; Compositions thereof; Preparation or purification thereof
    • C12N7/04—Inactivation or attenuation; Producing viral sub-units
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K2039/51—Medicinal preparations containing antigens or antibodies comprising whole cells, viruses or DNA/RNA
    • A61K2039/525—Virus
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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    • C12N2760/16111—Influenzavirus A, i.e. influenza A virus
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    • C12N2760/00011—Details
    • C12N2760/16011—Orthomyxoviridae
    • C12N2760/16111—Influenzavirus A, i.e. influenza A virus
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    • C12N2760/00011—Details
    • C12N2760/16011—Orthomyxoviridae
    • C12N2760/16111—Influenzavirus A, i.e. influenza A virus
    • C12N2760/16134—Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein
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    • C12N2760/00011—Details
    • C12N2760/16011—Orthomyxoviridae
    • C12N2760/16111—Influenzavirus A, i.e. influenza A virus
    • C12N2760/16151—Methods of production or purification of viral material
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    • C12N2760/00011—Details
    • C12N2760/16011—Orthomyxoviridae
    • C12N2760/16211—Influenzavirus B, i.e. influenza B virus
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    • C12N2760/16011—Orthomyxoviridae
    • C12N2760/16211—Influenzavirus B, i.e. influenza B virus
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    • C12N2760/16011—Orthomyxoviridae
    • C12N2760/16211—Influenzavirus B, i.e. influenza B virus
    • C12N2760/16234—Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein

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Abstract

The invention provides means, methods and use for producing a virus particle , including cells therefore and virus particles thus produced. One aspect of t he invention utilizes cells provided with nucleic acid encoding post- translational modification protein, thereby altering at least one property o f virus (being) produced by the cells compared to the un-manipulated cell.</SD OAB>

Claims (41)

1. A method for producing a virus particle, said method comprising the steps of:
- contacting a cell with a virus particle in a culture medium under conditions conducive to infection of said cell by said virus particle;
and - culturing said cell under conditions conducive to propagation of said virus particle, wherein said cell over-expresses a nucleic acid encoding an alpha2,6 sialyltransferase or a functional equivalent thereof.
2. A method according to claim 1, wherein said alpha2,6 sialyltransferase is human alpha2,6 sialytransferase.
3. A method for producing a virus particle, said method comprising the steps of:
- contacting a cell with a virus particle in a culture medium under conditions conducive to infection of said cell by said virus particle;
and - culturing said cell under conditions conducive to propagation of said virus particle, wherein said cell over-expresses a nucleic acid encoding an alpha2,3 sialyltransferase or a functional equivalent thereof.
4. A method according to claim 3, wherein said alpha2,3 sialyltransferase is human alpha2,3 sialytransferase.
5. A method according to any one of claims 1-4, wherein said virus particle is an influenza virus particle or an equivalent thereof.
6. A method according to claim 5, wherein said influenza virus particle is present in an influenza isolate.
7. A method according to claim 6, wherein said influenza isolate is obtained from at least one influenza-infected mammalian subject.
8. A method according to claim 7, wherein said influenza-infected mammalian subject is human or pig.
9. A method according to claim 6, wherein said influenza isolate is obtained from at least one influenza-infected bird.
10. A method according to any one of claims 1-9, wherein said cell is transformed with E1 from adenovirus.
11. A method according to claim 10, wherein said cell is a human cell.
12. A method according to claim 11, wherein said human cell is PER. C6 or a derivative thereof.
13. A method according to any one of claims 1-12, wherein said nucleic acid encoding the sialyltransferase is heterologous to said cell.
14. A method according to claim 13, wherein said nucleic acid encoding the sialyltransferase or functional equivalent is integrated into the genome of said cell.
15. A method for making a vaccine, said method comprising the steps of:
- producing a virus particle according to any one of claims 1-14; and - inactivating the virus particles so produced.
16. A method according to claim 15, wherein said method further comprises the steps of:
- treating said virus particles so produced to yield antigenic parts; and - obtaining at least one antigenic part.
17. A method according to claim 16, wherein said antigenic part comprises the hemagglutinin protein or a part thereof, and/or the neuraminidase protein or a part thereof, from influenza virus.
18. A vaccine obtainable according to any one of claims 15-17.
19. A pharmaceutical composition comprising a vaccine according to claim 18.
20. Use of a cell that over-expresses an alpha2,6 sialyltransferase or a functional part thereof for the propagation of a virus particle.
21. Use of a cell that over-expresses an alpha2,3 sialyltransferase or a functional part thereof for the production of a virus particle.
22. Use of a cell according to claim 20 or 21, wherein said virus particle is an influenza virus particle.
23. Use according to claim 22, wherein said influenza virus particle is present in an influenza isolate obtained from at least one influenza-infected mammalian subject.
24. Use according to claim 23, wherein said influenza-infected mammalian subject is a human or a pig.
25. Use according to claim 22, wherein said influenza virus particle is present in an influenza isolate obtained from at least one influenza-infected bird.
26. A method for selective propagation of a set of predetermined virus particles present in an isolate, wherein said set of predetermined virus particles has affinity for a specific glycosylation moiety present on a receptor, and wherein said isolate comprises in addition to said set also virus particles not having the predetermined specificity, said method comprising the steps of:
- incubating a cell which is capable of expressing and exposing said receptor comprising said specific glycosylation moiety, with said isolate in a culture medium under conditions conducive to infection of said cell by at least one virus particle present in said set;
- culturing said cell under conditions conducive to propagation of said virus particle; and - harvesting virus particles so produced from said cell and/or said culture medium.
27. A method according to claim 26, wherein said glycosylation moiety comprises a SAalpha2,6Gal residue.
28. A method according to claim 26, wherein said glycosylation moiety comprises a SAalpha2,3Gal residue.
29. A method according to any one of claims 26-28, wherein said set of predetermined virus particles is a set of predetermined influenza virus particles.
30. A method according to any one of claims 26-29, wherein said isolate is an influenza isolate.
31. A method according to claim 30, wherein said influenza isolate is obtained from at least one influenza-infected human, pig or bird,
32. A method according to any one of claims 26-31, wherein said cell is transformed with E1 from adenovirus.
33. A method according to claim 32, wherein said cell is a human cell.
34. A method according to claim 33, wherein said human cell is PER. C6 or a derivative thereof.
35. A method according to any one of claims 26-34, wherein said cell comprises a nucleic acid encoding a sialyltransferase that is heterologous to said cell.
36. A method according to claim 35, wherein said nucleic acid encoding a sialyltransferase is integrated into the genome of said cell.
37. A human cell comprising a heterologous nucleic acid encoding an alpha2,6 sialyltransferase.
38. A human cell comprising a heterologous nucleic acid encoding an alpha2,3 sialyltransferase.
39. A human cell according to claim 37 or 38, wherein said heterologous nucleic acid is integrated into the genome of said human cell.
40. Use of a human cell according to any one of claims 37-39 for the selective propagation of a virus particle.
41. Use of a human cell according to claim 40, wherein said virus particle is an influenza virus particle.
CA2468957A 2001-12-07 2002-12-09 Methods of propagation of influenza virus in cell lines over expressing sialyl transferases Expired - Lifetime CA2468957C (en)

Applications Claiming Priority (5)

Application Number Priority Date Filing Date Title
NLPCT/NL01/00892 2001-12-07
PCT/NL2001/000892 WO2003048197A1 (en) 2001-12-07 2001-12-07 Production and of viruses, viral isolates and vaccines
EP02075327 2002-01-25
EP02075327.3 2002-01-25
PCT/NL2002/000804 WO2003048348A2 (en) 2001-12-07 2002-12-09 Production of viruses, viral isolates and vaccines

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Publication Number Publication Date
CA2468957A1 true CA2468957A1 (en) 2003-06-12
CA2468957C CA2468957C (en) 2011-07-12

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CA2468957A Expired - Lifetime CA2468957C (en) 2001-12-07 2002-12-09 Methods of propagation of influenza virus in cell lines over expressing sialyl transferases

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US (2) US7504248B2 (en)
EP (1) EP1465987B1 (en)
JP (1) JP4480398B2 (en)
KR (1) KR100979025B1 (en)
CN (1) CN100547069C (en)
AT (1) ATE384785T1 (en)
AU (1) AU2002351444B2 (en)
CA (1) CA2468957C (en)
DE (1) DE60224843T2 (en)
ES (1) ES2297028T3 (en)
NZ (1) NZ533124A (en)
PT (1) PT1465987E (en)
WO (1) WO2003048348A2 (en)

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